For _______, initial recruitment of ovarian follicles is INDEPENDENT of hormones; subsequent growth of follicle and oocyte maturation depends on gonadotropins.

For ______, recruitment and oocyte maturation DEPENDENT on gonadotropins and sex steroids.

For birds and mammals, initial recruitment of ovarian follicles is INDEPENDENT of hormones; subsequent growth of follicle and oocyte maturation depends on gonadotropins.

For reptiles, amphibians, and fishes, recruitment and oocyte maturation DEPENDENT on gonadotropins and sex steroids.

LIVER

E2 made from follicular cell, acts on liver to produce vitellogenin, which gets uptaked by the follicular cell.

In vitellogenesis, theca cells are stimulated by ______ to produce _____.

_____ from theca cells enters _______ cells which is stimulated by ______ to produce ______.

That acts on the ______ to produce _______.

Just prior to oocyte maturation, the theca cells begin producing ______ which enters granulosa cells and is converted to ______. This causes oocyte maturation (GVBD) in ____.

In vitellogenesis, theca cells are stimulated by LH to produce Testosterone from cholesterol (steroidogenic cells).

Testosterone from theca cells enters granulosa cells which are stimulated by FSH to produce estradiol from testosterone.

Estradiol acts on the liver to produce vitellogenin.

Just prior to oocyte maturation, the theca cells being producing 17α-hydroxyprogesterone from cholesterol which enters granulosa cells and is converted to 17α,20β-dihydroxyprogesterone by 20β-hydroxylase. This causes OOCYTE MATURATION (GVBD) in fish.

Maturation inducing substances (MIS)-->____

And what is the MIS in

Mammals?

Frogs?

Fish?

How does MIS work?

MIS --> GVB

In mammals, it is progestin

In frogs, it is progesterone

MIS acts on the oocyte via membrane steroid receptors and induces the production of a maturation promoting factor (MPF).

What do maturation promoting factors (MPF) do?

What is it made by?

MPF induces mitosis or meiosis.

Made by 2 proteins:

Cyclin b (regulatory subunit - regulated by MIS)

Cdc2 kinase (catalytic subunit - constitutively expressed)

In preovulatory follicle in primates, which cells are stimulated by LH and which are stimulated by FSH?

What do these cells produce?

LH stimulates theca cells which produce androstenedione

FSH stimulates granulosa cells which produce estradiol

Steroidogenic factor 1 (SF1)

***

ESSENTIAL for tissues that make steroids!

SF1 KO mice do no develop adrenal glands or gonads.

Estradiol acts on granulosa cells to increase expression of LH receptors so that the follicle may respond to the LH surge.

***

Without E2, LH receptors do not develop on granulosa cells.

E2 and FSH cooperate to increase LH receptors on granulosa cells.

Granulosa lutein cells secrete...

Describe the pathway.

P4

Granulosa shifts from a steroid converting cell to a steroid synthesizing cell.

LH and FSH bind to LHRs and FSHRs and activate adenylate cyclase.

Increased cAMP activates SF1 which activates StAR (mediates uptake of cholesterol into mitochondria),

P450scc (converts cholesterol to PREGNENOLONE inside the mitochondria),

and 3betaHSDII converts pregnenolone to P4

***

LH receptors also important for maintaining P4 secretion.

Less estradiol is made from androstenedione than before.

Basal LH stimulates OMI activity

the LH surge decreases production of OMI

***

OMI arrests oocyte in prophase I

Decreased cAMP

Increased Ca2+

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Decreased cAMP and increased Ca2+ --> GVB

GnRH analogs can suppress pituitary gonadotropin release by binding to receptors for a long time so that they are internalized.

Also act directly on ovary to suppress steroidogenesis.

***

GnRH also produced in the ovaries.

Anti-estrogen:

Anti-progesterone:

Anti-androgen:

Anti-estrogen: Temoxifen

Anti-progesteron: Mifepristone (RU46)

Anti-androgen: Cyproterone acetate, Sprinolactone

Inhibition of gonadotropin secretion to block ovulation

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Morning after pill= high dose of prgestin - blocks ovulation

GnRH

***

Also synchronize estrous cycle with lactalase

Possible causes of anovulation

Possible treatments

Hypopituitarism

Lack of GnRH neuronal function

Prolactinomas (tumors in pituitary that hypersecrete PRL)

LH and FSH injections via menatropins (=uring from post-menopausal women containing LH and FSH) --> superovulation

hCG= LH-like --> ovulation

Do male rats exhibit lordosis when injected with E2 and P4?

What do female rats require in order to show lordosis?

NO

Females require priming by E2 ~24 hours before sexual activity

Describe organizational actions of sex steroids.

Describe activational actions of steroids.

Steroid hormones need to be present during some critical period in development.

They organize sex-specific wiring in the brain - when a setoird is produced later in life (i.e. puberty), the animal can respond to it (programmed).

Production of steroids later activates sex-specific behavior. In order to get a male to respond as a female later in life, need to be exposed to a certain amount of steroids EARLY in life.

What steroids are male sexual behaviors ORGANIZED and ACTIVATED by?

What steroids are female sexual behaviors ORGANIZED and ACTIVATED by?

Male sexual behavior ORGANIZED by androgens and ACTIVTATED by androgens.

Female sexual behavior ORGANIZED by LACK of steroids and ACTIVATED by estrogens and progesterins.

Actions of testosterone may depend on conversion to estrogen w/in the brain for masculinization. The brain expresses a lot of aromatase.

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Alpha-fetal protein binds E2 but NOT T. So E2 cannot enter the brain but T can...T gets converted to E2 in the brain by aromatase.

**The ACTIVATIONAL actions of androgens probably do NOT require conversion to E2 (these are androgen receptor-mediated actions).

____ produced by cloacal gland of male newt (cynops pyrrhogaster) = sexual attractant

____ produced by cloacal gland of male newt (cynops ensicauda)

____= pheomone made by female goldfish that increases male _______

Sodefrin produced by cloacal gland of male newt (cynops pyrrhogaster) = sexual attractant and decapeptide --> courtship behavior.

Silefrin produced by cloacal gland of male newt (cynops ensicauda)

17alpha,20betaP= pheromone made by female goldfish that increases male LH and semen production

Name the two types of tissue of the placenta.

How long after fertilization does placenta develop?

Decidua= tissue from mother

Trophoblast= tissue from fetus

Placenta develops ~8-9wks after fertilization.

1. Endocrine - secretes steroid and protein hormones (majority from trophoblast).

Decidua --> RPL, Relaxin, and Prostaglandins

2. Participates in control of fetal endocrine function, growth, and development - Respiratory organ, excratory organ, and alimentary organ.

3. Selecive barrier to govern maternal and fetal systems interactions - environment w/in mother is "growth inhibitory" (insulin resistant and no tissue growth).

Polypeptide hormones can NOT pass through placenta, but small molecules like steroids and TH can.

hCG= glycoprotein hormone (like LH and FSH) - LH-like activity (beta subunit more like that in LH than FSH).

Used to induced ovulation in women primed with LH and FSH.

Long t1/2 ~24hrs (much longer than other glycoproteins).

2X concentration every 2 days in 1st 6wks of pregnancy.

**Plays role in maintaining corpus luteum and controlling P4 levels.

[hCG] levels in fetus ~1% of that in maternal circuation.

Placental lactogen - similar structure to PRL and GH. ONLY made by the placenta.

Promotes growth-inhibitory environment of the mother.

Others: POMC peptides (ACTH, endorphins), CRH, CRHBP, GnRH (same as hypothalamic GnRH - may control hCG release), TRH, FGF, EGF, PDGF, IGFs.

Does the placenta make steroids?

What steroid-converting enzyme is highly expressed in the placenta?

NO, the placenta is a steroid-converting organ.

Lots of aromatase (androgens-->estrogen).

***

No aromatase, get pseudohermaphroditism in genetically female fetus.

"Big baby syndrome"

How does maternal plasma [amino acid] affect baby?

Macrosomia - 2X chance of being obese later

Plasma [amino acid] has positive correlation with fetal growth.

How does E2 and P4 change near the end of pregnancy?

How does this change in E2 affect pregnancy?

Late in pregnancy, E2 increases above P4 and P4 decreases a bit.

Rise in E2 -->

1. Increased oxytocin receptors

2. Increased synthesis of connexins

3. Increased synthesis of prostaglandins - prostaglandins --> increased collagenase which breaks down collagen which "ripens" the cervix

Lesioning of the PVN = lesioning of CRF neurons --> greatly extends gestation

***

CRF signals end of gestation.

Fetal CRF signals to the pituitary which releases ACTH which signals to the fetal adrenal cortex which secretetes DHEA-S which is converted to E2.